title: Highly accurate detection of ovarian cancer using CA125 but limited improvement with serum matrix-assisted laser desorption/ionization time-of-flight mass spectrometry profiling.
abstract: Our objective was to test the performance of CA125 in classifying serum samples from a cohort of malignant and benign ovarian cancers and age-matched healthy controls and to assess whether combining information from matrix-assisted laser desorption/ionization (MALDI) time-of-flight profiling could improve diagnostic performance.
  
  
  
  Serum samples from women with ovarian neoplasms and healthy volunteers were subjected to CA125 assay and MALDI time-of-flight mass spectrometry (MS) profiling. Models were built from training data sets using discriminatory MALDI MS peaks in combination with CA125 values and tested their ability to classify blinded test samples. These were compared with models using CA125 threshold levels from 193 patients with ovarian cancer, 290 with benign neoplasm, and 2236 postmenopausal healthy controls.
  
  
  
  Using a CA125 cutoff of 30 U/mL, an overall sensitivity of 94.8% (96.6% specificity) was obtained when comparing malignancies versus healthy postmenopausal controls, whereas a cutoff of 65 U/mL provided a sensitivity of 83.9% (99.6% specificity). High classification accuracies were obtained for early-stage cancers (93.5% sensitivity). Reasons for high accuracies include recruitment bias, restriction to postmenopausal women, and inclusion of only primary invasive epithelial ovarian cancer cases. The combination of MS profiling information with CA125 did not significantly improve the specificity/accuracy compared with classifications on the basis of CA125 alone.
  
  
  
  We report unexpectedly good performance of serum CA125 using threshold classification in discriminating healthy controls and women with benign masses from those with invasive ovarian cancer. This highlights the dependence of diagnostic tests on the characteristics of the study population and the crucial need for authors to provide sufficient relevant details to allow comparison. Our study also shows that MS profiling information adds little to diagnostic accuracy. This finding is in contrast with other reports and shows the limitations of serum MS profiling for biomarker discovery and as a diagnostic tool.
authors.affiliation: BioCentre and Department of Chemistry, University of Reading, Reading, United Kingdom.
authors.forename: Ali
authors.initials: A
authors.lastname: Tiss
authors.forename: John F
authors.initials: JF
authors.lastname: Timms
authors.forename: Celia
authors.initials: C
authors.lastname: Smith
authors.forename: Dmitry
authors.initials: D
authors.lastname: Devetyarov
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Stephane
authors.initials: S
authors.lastname: Camuzeaux
authors.forename: Brian
authors.initials: B
authors.lastname: Burford
authors.forename: Ilia
authors.initials: I
authors.lastname: Nouretdinov
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ford
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Luo
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
authors.forename: Alex
authors.initials: A
authors.lastname: Gammerman
authors.forename: Rainer
authors.initials: R
authors.lastname: Cramer
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood; D001774:Blood Chemical Analysis; D018394:CA-125 Antigen / Q000032:analysis* / Q000097:blood; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D055088:Early Detection of Cancer / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis* / Q000097:blood; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood / Q000145:classification / Q000175:diagnosis; D010051:Ovarian Neoplasms / Q000097:blood / Q000145:classification / Q000175:diagnosis; D058996:Quality Improvement; D012016:Reference Values; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D054928:Validation Studies as Topic
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; C451759:MUC16 protein, human; D008565:Membrane Proteins